Transport of bestatin in rat renal brush-border membrane vesicles

Biochem Pharmacol. 1993 May 5;45(9):1763-8. doi: 10.1016/0006-2952(93)90431-u.


Bestatin [(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl-L-leucine] is a dipeptide, comprising L-leucine and an unusual beta-amino acid. We studied its transport mechanism in rat renal brush-border membrane vesicles. Uptake of cephradine, an aminocephalosporin, by isolated brush-border membrane vesicles was trans-stimulated and cis-inhibited by bestatin, indicating that these drugs are transported via the same transport system(s). The uptake of bestatin was trans-stimulated by preloading the vesicles with glycylsarcosine, and was cis-inhibited by substrates for the H+/dipeptide cotransport system. Bestatin inhibited tetraethylammonium (an organic cation) uptake, and bestatin uptake was cis-inhibited by substrates for the H+/organic cation antiport system. In addition, bestatin uptake was stimulated by an outward H+ gradient (the driving force for the H+/organic cation antiport system). These findings suggest that bestatin, in spite of being a dipeptide, is transported via not only the H+/dipeptide cotransport system but also the H+/organic cation antiport system in rat renal brush-border membrane.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Cephradine / metabolism
  • Dipeptides / pharmacology
  • Glycylglycine / pharmacology
  • Hydrogen-Ion Concentration
  • Kidney / metabolism*
  • Leucine / analogs & derivatives*
  • Leucine / metabolism
  • Leucine / pharmacology
  • Male
  • Microvilli / metabolism*
  • Rats
  • Rats, Wistar
  • Tetraethylammonium
  • Tetraethylammonium Compounds / pharmacology


  • Dipeptides
  • Tetraethylammonium Compounds
  • Glycylglycine
  • glycylsarcosine
  • Tetraethylammonium
  • Cephradine
  • Leucine
  • ubenimex